Biomedical subjects

M Kojiro

Publications and source records attributed to M Kojiro.

At least 55 records · Page 3Linked to original sources

PubMed1998

p53 overexpression in small hepatocellular carcinomas containing two different histologic grades.

There is evidence to suggest that a focus of less-differentiated hepatocellular carcinoma (HCC) may arise within a pre-existing well-differentiated HCC, eventually replacing it. In the present study, the p53 tumor suppressor gene was analyzed by immunohistochemistry in 31 hepato-cellular carcinomas (HCCs) containing two or more regions in the same nodule with different histologic grades. p53 was overexpressed in the nucleus in 13 of 31 HCCs (42%), in seven of which p53 overexpression was seen only in the less-differentiated area of the tumor. This suggests that overexpression of presumed mutant p53 may have contributed to dedifferentiation during the development of HCC.

Adult↗

PubMed1998

Pathology of early hepatocellular carcinoma: progression from early to advanced.

Small, early stage hepatocellular carcinoma (HCC) can be divided into 2 types; small nodular HCC with distinct margins and small HCC with indistinct margins. The latter consists of well-differentiated cancerous tissue with replacing growth at the boundary and with many portal tracts retained in the tumor. When these tumors reach approximately 1.5-2.0 cm in diameter, moderately or poorly differentiated cancer tissues develop within the well-differentiated cancer tissue and well-differentiated cancer tissues are replaced by less differentiated cancer tissues. This dedifferentiation seems to be closely related to tumor proliferation. When less differentiated cancer tissues within the well-differentiated cancer nodules proliferate in an expansive fashion, a "nodule in nodule" appearance is frequently identified. On the other hand, small nodular HCCs with distinct margins are well-defined, with more than half of them encapsulated by a thin fibrous capsule, and about 60% moderately differentiated. Tumor invasion into the portal vein and intrahepatic metastasis are found in 27% and 10%, respectively. Thus, although the size of the tumor may be small, some distinctly nodular small HCCs can already be interpreted as advanced cancers.

Carcinoma, Hepatocellular↗

PubMed1997

CD4+ hepatic cancer-specific cytotoxic T lymphocytes in patients with hepatocellular carcinoma.

We investigated T cell immunity against hepatocellular carcinoma (HCC), and showed that both peripheral blood mononuclear cells and tumor-infiltrating lymphocytes incubated with interleukin-2 alone displayed HLA-nonrestricted but hepatic cancer-specific cytotoxicity in a majority of patients with HCC. Namely, they lysed both HCC and cholangiocellular carcinomas in an HLA-nonrestricted manner, but they did not lyse any tumors with the other histological types tested, normal hepatocytes, or the cells transfected with hepatitis C virus or MUC1 gene. These CTL lines and clones were phenotypically CD3+CD4+CD8-. These unique CTL could play important roles in T cell immunity against HCC.

CD4-Positive T-Lymphocytes↗

PubMed1997

Long-term evolution of fibrosis from chronic hepatitis to cirrhosis in patients with hepatitis C: morphometric analysis of repeated biopsies.

To clarify the characteristics of fibrosis developed in the process from chronic hepatitis C to cirrhosis, a morphometric analysis of liver biopsy samples was conducted on 25 chronic hepatitis C patients and 20 chronic hepatitis B patients (controls). Hepatitis C patients were followed up for 3 to 23 years. The mean number of liver biopsies performed on these patients was 3.8. Each biopsy was evaluated for the degree of fibrosis by using two methods: a semiquantitative method with a staging scoring system, and morphometry using a computed image analysis system. A significant correlation was observed between the Stage and the area of fibrosis (AF = the ratio of the area of fibrosis to that of the entire tissue specimen). The AF in cirrhosis was significantly higher in hepatitis C patients than in hepatitis B patients. The ratio of AF in the last biopsy sample to AF in the initial biopsy sample was significantly higher in hepatitis C patients than in hepatitis B patients. Evolution from chronic hepatitis C to cirrhosis occurred more frequently in patients aged > or = 50 years, and this time period was 1.8 times shorter than that in patients aged < 50 years. AF in the initial biopsy related significantly to the period of evolution from chronic hepatitis C to cirrhosis. AF in the initial biopsy might be a predictive factor for prognosis.

Adult↗

PubMed1997

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Adolescent↗

PubMed1997

Transmission routes and clinical courses in sporadic acute hepatitis C.

Between March 1994 and March 1996 we studied transmission routes and clinical courses in eight patients with sporadic acute hepatitis C (two men, six women). Of the eight patients, three were treated for another illness 1-2 months before the onset of hepatitis, one was a parenteral drug abuser, one had an accidental needlestick injury and two had sexual contact with a partner with chronic hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV RNA and alanine aminotransferase (ALT) became persistently negative without treatment, and four men and two women with the same results following interferon (IFN) treatment. It is thought that IFN therapy may prevent the progression to chronic liver disease. Results from this study might be useful in the future management of patients with sporadic acute hepatitis C.

Acute Disease↗

PubMed1997

Apoptosis in the pancreas of genetically diabetic rats with a disrupted cholecystokinin (CCK-A) receptor gene.

In a previous study, we reported that the pancreatic wet weight in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, cholecystokinin-A (CCK-A) receptor-defective because of a congenital gene abnormality, was significantly lower than in control rats (Long-Evans Tokushima Otsuka; LETO) from 3 weeks of age. In this study we examined apoptosis of pancreatic acinar cells in OLETF rats at 5 to 6 weeks of age in comparison with that in LETO rats. We present here direct morphologic evidence of apoptosis in OLETF rats, using a 3'-OH nick end-labeling method for detecting cells with DNA strand breaks and electron microscopy. Nick end-labeling revealed a small number of positively labeled acinar cells in OLETF rats. On electron microscopic examination, small numbers of apoptotic cells were seen in the lobules in OLETF rats but not in LETO rats. These results suggest that apoptosis plays an important role in the destruction of acinar cells of OLETF rats and induces atrophy of the pancreas.

Animals↗

PubMed1997

Detection of MAGE-4 protein in the sera of patients with hepatitis-C virus-associated hepatocellular carcinoma and liver cirrhosis.

The aim of this study was to determine whether MAGE-4 protein is detectable in sera of patients with hepatocellular carcinoma and other liver diseases. An enzyme-linked immunosorbent assay was employed for detection of MAGE-4 protein in sera of liver disease patients, healthy men and women (control I) and those undergoing prostatic cancer screening (control II). MAGE-4 protein levels in sera of patients with hepatitis C virus-associated HCC (HCC-C) (n = 45, mean = 2.160 ng/ml) and HCV-associated cirrhosis (LC-C) (n = 55, 1.072 ng/ml) were significantly higher (P < 0.0001) than those of control I (0.327 ng/ml) or control II (0.394 ng/ml). MAGE-4 protein was positive in 21/45 (46.7%) HCC-C patients and 18/55 (32.7%) LC-C patients (cut-off, mean plus 2 SD in healthy controls) but in 0/12 (0%) hepatitis B virus-associated HCC (HCC-B) patients, 3/49 (6.1%) hepatitis B virus-associated LC (LC-B) patients, 4/47 (8.5%) alcoholic liver disease patients, and 1/49 (2.0%) controls. Serum MAGE-4 protein level may be useful as a marker for identification of LC-C patients suffering from HCC that is undetectable by presently available methods.

Adult↗

PubMed1997

Hepatitis C virus RNA present in saliva but absent in breast-milk of the hepatitis C carrier mother.

In order to examine whether saliva and breast-milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast-milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1- to 3-months intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast-milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast-milk is not likely to be a source of mother-to-child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.

Child, Preschool↗

PubMed1997

alpha-Fetoprotein-producing rectal carcinoma--a case report.

A case with an alpha-fetoprotein (AFP)-producing carcinoma originating from the rectum is described. A 71-year-old male patient, who underwent a rectectomy for rectal carcinoma, developed space occupying lesions in the liver and a remarkable AFP elevation (220,000 ng/ml) in the 6th month postoperatively, and then expired one year later. Histologically, the rectal carcinoma consisted of well-differentiated adenocarcinomas, and contiguous cancerous cells proliferating in either a medullary or trabecular pattern. In the "trabecular" areas, localization of AFP was confirmed immunohistochemically. Results of concanavalin A or lens culinaris agglutinin affinity chromatography demonstrated that it was between a hepatic type and a yolk sac type, and was considered to be an intestinal type. This could have been an AFP-producing rectal carcinoma, in which the patient experienced liver metastasis at a relatively early postoperative period and died. This shows that AFP-producing rectal carcinomas are highly malignant, biologically, similar to AFP-producing gastric cancers.

Adenocarcinoma↗

PubMed1997

A case of malignant lymphoma with hemophagocytic syndrome presenting as hepatic failure.

We report the case of a 50-year-old female with malignant lymphoma presenting hemophagocytic syndrome and liver failure. She developed high fever, marked jaundice, and progressive liver failure, followed by evidence of disseminated intravascular coagulation (DIC). The course was complicated by severe hepatitis and the patient died six days after admission. Pathological diagnosis on autopsy specimens of the lung hilar lymph nodes was non-Hodgkin's T cell lymphoma, of the diffuse small cell type. Histopathologic examination of the liver demonstrated diffuse liver cell destruction with prominent T lymphocyte infiltration in the portal and periportal area. In addition to marked lymphoma cell infiltration, hemophagocytosis by prominent infiltrative macrophages was observed in various organs, such as the liver and bone marrow, indicating the hemophagocytic syndrome. The hemophagocytic syndrome characterized in the present case may have been responsible for the extremely rapid and fulminant course.

Fatal Outcome↗

PubMed1997

A new human hepatocellular carcinoma cell line (HAK-2) forms various structures in collagen gel matrices.

We established a new human hepatocellular carcinoma (HCC) cell line, designated HAK-2, from a surgically resected HCC of a 57-yr-old Japanese man. The patient's tumor consisted of 5 different histological features in a single nodule: well-differentiated HCC with trabecular pattern; and moderately differentiated HCC with 4 different patterns (i.e., trabecular, pseudoglandular, solid, and scirrhous). Morphologically, HAK-2 cells on a plastic dish showed oval-shaped nuclei and large flat, polygonal eosinophilic cytoplasm and proliferated in a monolayered sheet with a population doubling time of 36.8 hours. Meanwhile, various structures, such as compact, trabecular, and tubular arrangements, were induced in HAK-2 cells cultured in type I collagen gel matrix. Also, HAK-2 cells in vitro underwent spontaneous apoptosis more frequently than other HCC cell lines examined. HAK-2 cells secreted various plasma proteins including albumin into the culture medium. Chromosome and flow cytometric analyses revealed that HAK-2 had many structural abnormalities with human karyotype and a single aneuploid cell population with a DNA index of 3.7, respectively. These findings suggest that HAK-2 is a new human HCC cell line representing two morphological characteristics; (1) formation of various structures in the presence of extracellular matrix and (2) frequent spontaneous apoptosis in vitro.

Aneuploidy↗

PubMed1996

A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that shows the features of hepatocellular carcinoma or cholangiocarcinoma under different growth conditions.

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma is a rare tumor of the liver, and its histogenesis remains unclear. The authors addressed this issue in the current article. METHODS: A specimen aseptically obtained from the surgically resected combined hepatocellular and cholangiocarcinoma was processed for primary culture. The morphologic features of the established cell line cultured on a plastic dish and in type I collagen gel matrix, and transplanted in nude mice were examined. RESULTS: The authors established a new human combined hepatocellular and cholangiocarcinoma cell line, designated KMCH-2, from a 40-year-old Japanese man. KMCH-2 cells on a plastic dish proliferated in a monolayered sheet with a population doubling time of 32 to 44 h. KMCH-2 expressed functional characteristics of hepatocellular carcinoma, such as albumin synthesis at protein and mRNA levels, but were poorly differentiated in morphology, showing an overlap of features with cholangiocarcinoma. KMCH-2 cells cultured within type I collagen gel matrix proliferated, forming compact to vaguely trabecular and pseudoglandular arrangements, and differentiated to show morphological characteristics of hepatocellular carcinoma unlike the cells on a plastic dish. Mucin production was not detected in KMCH-2 cells in vitro. Subcutaneous tumors which developed in nude mice injected with KMCH-2 cells represented features of adenocarcinoma with mucin production. CONCLUSIONS: The present results revealed the presence of an albumin-producing human hepatic neoplastic cell, such as KMCH-2, that can differentiate to show not only the features of hepatocellular carcinoma but also those of cholangiocarcinoma under certain growth conditions.

Adult↗

PubMed1996

Expression of Fas and anti-Fas-mediated apoptosis in human hepatocellular carcinoma cell lines.

BACKGROUND/AIMS: Fas transduces apoptotic signals upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. Because little is known about Fas expression and function in hepatocellular carcinoma, these issues are addressed in the current article. METHODS: We examined Fas expressions at protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, on six hepatocellular carcinoma cell lines. RESULTS: Two cell lines constitutively expressed high levels of Fas both on their cell surface and in their cytoplasm, whereas the other four cell lines expressed Fas mainly in their cytoplasm. Fas mRNA of normal size was detected in all cell lines in reverse transcriptase-polymerase chain reaction analyses. Although a Fas mRNA variant, suggesting a soluble Fas molecule, was detected in the two cell lines expressing high levels of Fas, its amount was very small compared to that of normal-sized Fas transcript. Anti-Fas dose-dependently induced apoptosis exclusively in the two cell lines which constitutively express high levels of cell surface Fas. However, after preincubation with interferon-gamma, one cell line with low surface Fas expression became anti-Fas sensitive equivalent to the two cell lines expressing surface Fas at high levels. Studies of two clonally related cell lines showed that dedifferentiated clones had lower Fas expression and resistance to anti-Fas, suggesting deterioration of Fas system after clonal cell dedifferentiation. CONCLUSIONS: These findings suggest sensitivity to anti-Fas is virtually relevant to cell surface Fas, but not to cytoplasmic Fas expression. However, its expression level does not correlate to sensitivity to anti-Fas.

Antineoplastic Agents↗

PubMed1996

Expressions of basic fibroblast growth factor and its receptors and their relationship to proliferation of human hepatocellular carcinoma cell lines.

On six human hepatocellular carcinoma (HCC) cell lines (KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, and HAK- 1B), we examined expressions and functions of the proteins and messenger RNAs (mRNAs) of basic fibroblast growth factor (bFGF) and its receptor, i.e., fibroblast growth factor receptor-1 (FGFR-1), as well as mRNA expressions of FGFR-2 approximately 4. All six cell lines expressed the proteins and mRNAs of bFGF and FGFR-1, and at least one of FGFR-2 approximately 4 mRNAs. Two of the six cell lines (KYN-1 and KYN-3) presented significant release of bFGF in culture supernatant, while the release in the remaining four cell lines was quite small. Addition of anti-bFGF neutralizing antibody (1, 10, or 20 microg/mL) to culture medium resulted in marked suppression of cell proliferation in all cell lines except HAK-1A. On the other hand, addition of exogenous bFGF (0.1, 1, or 5 ng/mL) to culture medium stimulated cell proliferation except in KIM-1 and KYN-2. When KIM-1 was transplanted to nude mice and anti-bFGF antibody was injected subcutaneously to a space surrounding the developed tumor, tumor proliferation was significantly suppressed in nude mice that received anti-bFGF antibody than in control mice, but there were no histological differences between the groups, including blood space formation in the stroma. In conclusion, hepatocellular carcinoma (HCC) cells may possess a proliferation mechanism regulated by an autocrine mechanism, a paracrine mechanism, or both, which are mediated by bFGF/FGFR.

Animals↗

PubMed1996

Pathomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver.

A pathomorphological study was conducted to clarify the localization of Kupffer cells in hepatocellular carcinoma (HCC) tissues and such hyperplastic nodular lesions as adenomatous hyperplasia (AH) and focal nodular hyperplasia (FNH). Materials were surgical specimens of 50 HCCs, 7 AHs, and 13 FNHs. These tissues were immunohistochemically stained with an anti-human macrophage antibody (anti-CD68 antibody). Among CD68-positive cells, short spindle-shaped cells were considered as Kupffer cells, and Kupffer cell numbers in tumor lesions and surrounding liver tissues of each specimen were comparatively examined. As a result, the number of Kupffer cells in well-differentiated HCC tissues less than 1 cm in diameter was 27.8 +/- 3.3 (mean +/- SE/025 mm2); in noncancerous tissues, it was 302 +/- 3.2, showing no statistically significant differences. The number of Kupffer cells in cancerous tissues decreased in comparison with the number in noncancerous tissues, as the tumor size increased and histological grade decreased. In hyperplastic nodular lesions, the number was higher in nodular lesions than in the surrounding liver tissues in 4 of 7 AHs (57.1%) and 6 of 13 FNHs (46.2%). This could explain the reason why enhanced MRI, which utilizes the selective taken-up mechanism of chondroitin sulfate iron colloid and superparamagnetic iron oxide into the reticuloendothelial system of the liver and spleen, depicts well-differentiated HCC and AH at the same signal intensity as in the surrounding liver tissues. Our findings also indicate that there is a limitation in differentiating or diagnosing small HCC and hyperplastic nodular lesions by using enhanced MRI, which utilizes Kupffer cell functions.

Carcinoma, Hepatocellular↗

PubMed1996

A clinicopathological study on combined hepatocellular and cholangiocarcinoma.

We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in our subjects, who had primary liver cancer and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant type (resembles CC 34%). The separated and HCC-predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.

Aged↗

PubMed1996

Clinicopathologic study on clear cell hepatocellular carcinoma.

In order to study the clinicopathologic characteristics of the clear cell variant of hepatocellular carcinoma (HCC), 215 consecutive cases measuring less than 5 cm in diameter were reviewed. The cases were divided into clear cell HCC (20 cases); focal clear cell HCC (77 cases); and non-clear cell HCC (118 cases). Clinical and pathological findings were compared among these groups. Clear cell HCC was moderately differentiated in 80% of cases and the incidence was not related to tumor size. The male to female ratio was 2.3:1, lower than the 6.9:1 of non-clear cell HCC. The association rate with liver cirrhosis was 90%, higher than the 59.3% of non-clear cell HCC. Three- and five-year survival rates, and no recurrence time were 54.5%, 33.3%, and 564 days, respectively, lower than the findings of 74.3%, 46.1%, and 770 days for non-clear cell HCC. But there is no significant difference in prognosis between both groups. Ultrastructurally, clear cells showed abundant glycogen storage and a variable degree of fat vacuoles, with a marked reduction of the number and size of organelles in the 8 cases examined. Non-clear cells of focal clear cell and non-clear cell HCC showed a moderate degree of glycogen storage in 85.7% and 28.6% of the seven cases examined from each group, with significant difference. It was concluded that clear cell HCC occurs mostly in the moderately differentiated form and is characterized by high female prevalence, high rate of association with liver cirrhosis, and has no significant difference in prognosis compared with non-clear cell HCC.

Adenocarcinoma, Clear Cell↗